Cutibacterium acnes is a dominant member of the human skin microbiota and is closely associated with the pathogenesis of acne vulgaris. The increasing emergence of antibiotic-resistant C. acnes strains has raised concerns regarding the long-term effectiveness of current therapies. This study aimed to characterize antibiotic susceptibility patterns and genomic features of C. acnes isolates obtained from healthy individuals and acne patients with different disease severities. A total of 45 participants were enrolled, including healthy controls and patients with mild and moderate-severe acne. C. acnes isolates recovered from pilosebaceous follicles were subjected to antibiotic susceptibility testing using the Kirby-Bauer disk diffusion method against five antibiotics including clindamycin, tetracycline, azithromycin, trimethoprim-sulfamethoxazole (TMP-SMX), and doxycycline. Representative isolates were selected for whole-genome sequencing, followed by multi-locus sequence typing (MLST) and antimicrobial resistance gene annotation. The results showed that most isolates remained highly susceptible to tetracycline-class antibiotics and TMP-SMX, whereas resistance to macrolides and clindamycin was detected, particularly among moderate-severe acne isolates. Genomic analysis revealed notable genetic diversity among the isolates and identified a single antimicrobial resistance gene, erm(51), consistent with the observed resistance phenotype. Overall, antimicrobial resistance in the analyzed C. acnes population was limited but detectable. The integration of phenotypic susceptibility testing with whole-genome analysis provides valuable insights for antimicrobial resistance surveillance and supports rational antibiotic use in acne management.